Metabolomic profiles delineate potential roles for gadolinium chloride in the proliferation or inhibition of Hela cells

Long, Xiaohui; Yang, Pengyuan; Liu, Qiong; Yao, Jun; Wang, Yi; He, Guohua; Hong, Guangyan; Ni, Jiazuan

doi:10.1007/s10534-011-9419-4

Cited by 9 publications

(3 citation statements)

References 35 publications

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“…Iron involvement in Gd (III) toxicity is in line with the transmetallation theory, by which endogenous metals, like iron, zinc, copper, magnesium, or calcium, attract the ligand, replacing gadolinium with the release of free Gd (III), which may deposit in different tissues. Finally, metabolic dysfunction, affecting lipid metabolism [38,52], and glycolytic and redox metabolic pathways were also highlighted [81]. Tubulin was pointed to as a potential Gdbinging protein, at least in the NIH-3T3 cells (mouse embryonic fibroblasts); this binding might inhibit the assembling of tubulin or depolymerize microtubules in cells [44].…”

Section: Reference Study Design Main Findingsmentioning

confidence: 99%

Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents—A Review

Coimbra,

Rocha,

Sousa

et al. 2024

IJMS

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Gadolinium-based contrast agents (GBCAs) have been used for more than 30 years to improve magnetic resonance imaging, a crucial tool for medical diagnosis and treatment monitoring across multiple clinical settings. Studies have shown that exposure to GBCAs is associated with gadolinium release and tissue deposition that may cause short- and long-term toxicity in several organs, including the kidney, the main excretion organ of most GBCAs. Considering the increasing prevalence of chronic kidney disease worldwide and that most of the complications following GBCA exposure are associated with renal dysfunction, the mechanisms underlying GBCA toxicity, especially renal toxicity, are particularly important. A better understanding of the gadolinium mechanisms of toxicity may contribute to clarify the safety and/or potential risks associated with the use of GBCAs. In this work, a review of the recent literature concerning gadolinium and GBCA mechanisms of toxicity was performed.

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Section: Reference Study Design Main Findingsmentioning

confidence: 99%

Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents—A Review

Coimbra,

Rocha,

Sousa

et al. 2024

IJMS

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“…We analyzed the in vitro cytotoxic effect of β-CD ligand 5 in two available mammalian tumoral cell lines in our group, HeLa cervix and HepG2 hepatic-carcinomas, using the MTT assays. 35 When grown in Dulbecco's modified eagle's medium (DMEM) supplemented with 10% calf serum without antibiotics at 37 °C (see the Supporting Information), both cell lines only showed a slight cytotoxic effect (20−40% inhibition) at concentrations of β-CD ligand 5 higher than 1 mM after 24 h of treatment, suggesting that β-CD ligand 5 is fairly nontoxic (see Figure 4).…”

Section: ■ Studies Of Protonation Of Ligandmentioning

confidence: 99%

Synthesis and Unprecedented Complexation Properties of β-Cyclodextrin-Based Ligand for Lanthanide Ions

et al. 2018

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Here, we report the synthesis and detailed studies on the coordination chemistry of a novel chemically modified polyaminocarboxylate (5) based on β-cyclodextrin (CD) scaffold for lanthanides. The target ligand is prepared in a highly efficient manner (seven total steps) from β-CD using the readily available iminodiacetic acid as a starting material. A propargyl group is attached to the iminodiacetate via N-alkylation, and the obtained derivative is efficiently conjugated to the β-CD scaffold via the copper(I)-mediated 1,3-dipolar cycloaddition. The generated 1,2,3-triazolmethyl residues advantageously provide a competent chelating group while displacing the metal coordination center away from the primary rim of β-CD, to afford the required conformational flexibility. The functional groups from each of the two adjacent glucopyranosyl units of β-CD complete a uniquely created octavalent coordination sphere for lanthanides while still sparing one site for dynamic water coordination. To help study the coordination chemistry of CD ligand 5, we also design a relevant maltoside ligand 6, which faithfully represents one submetal-binding section of ligand 5. Thanks to HRMS and NMR studies, we successfully elucidate the coordination chemistries of synthesized ligands. The octavalent coordination sphere of ligand 5 shows strong binding affinity to lanthanides. By potentiometric titration experiments, ligand 5 is found to bind gadolinium(III), forming 1:1, 1:2, and 1:3 multinuclear complexes with lanthanides, thus possessing great capacity for catalyzing the dynamic water-exchange. Further NMR studies also reveal that the formed ligand 5/Gd(III) complexes show significantly better abilities to alter T1 relaxivities of coordinated water than DOTA-Gd(III) and also some of the synthetic CD probes reported in the literature.

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“…The rare earth metals of Lanthanides (Lns) exhibit a variety of physical or chemical properties and have been applied in agriculture and medicine for a long time (15,16). Gadolinium (Gd), a member of Lns family, has multi-biological effects on organisms (17), and its compounds have important applications in magnetic resonance imaging (MRI) as contrast medium and are potential anticancer agents (18,19). In clinic, chelates of Gd such as gadobenate dimeglumine (MultiHance) are used as contrast agent in MRI (20).…”

Section: Gadolinium Chloride Elicits Apoptosis In Human Osteosarcoma mentioning

confidence: 99%

Gadolinium chloride elicits apoptosis in human osteosarcoma U-2 OS cells through extrinsic signaling, intrinsic pathway and endoplasmic reticulum stress

Tsai¹,

Huang²,

Chiang³

et al. 2016

Oncology Reports

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Gadolinium (Gd) compounds are important as magnetic resonance imaging (MRI) contrast agents, and are potential anticancer agents. However, no report has shown the effect of gadolinium chloride (GdCl3) on osteosarcoma in vitro. The present study investigated the apoptotic mechanism of GdCl3 on human osteosarcoma U-2 OS cells. Our results indicated that GdCl3 significantly reduced cell viability of U-2 OS cells in a concentration-dependent manner. GdCl3 led to apoptotic cell shrinkage and DNA fragmentation in U-2 OS cells as revealed by morphologic changes and TUNEL staining. Colorimetric assay analyses also showed that activities of caspase-3, caspase-8, caspase-9 and caspase-4 occurred in GdCl3-treated U-2 OS cells. Pretreatment of cells with pan-caspase inhibitor (Z-VAD-FMK) and specific inhibitors of caspase-3/-8/-9 significantly reduced cell death caused by GdCl3. The increase of cytoplasmic Ca2+ level, ROS production and the decrease of mitochondria membrane potential (ΔΨm) were observed by flow cytometric analysis in U-2 OS cells after GdCl3 exposure. Western blot analyses demonstrated that the levels of Fas, FasL, cytochrome c, Apaf-1, GADD153 and GRP78 were upregulated in GdCl3-treated U-2 OS cells. In conclusion, death receptor, mitochondria-dependent and endoplasmic reticulum (ER) stress pathways contribute to GdCl3-induced apoptosis in U-2 OS cells. GdCl3 might have potential to be used in treatment of osteosarcoma patients.

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Metabolomic profiles delineate potential roles for gadolinium chloride in the proliferation or inhibition of Hela cells

Cited by 9 publications

References 35 publications

Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents—A Review

Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents—A Review

Synthesis and Unprecedented Complexation Properties of β-Cyclodextrin-Based Ligand for Lanthanide Ions

Gadolinium chloride elicits apoptosis in human osteosarcoma U-2 OS cells through extrinsic signaling, intrinsic pathway and endoplasmic reticulum stress

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